Zeki Karasu

Ege University, İzmir, Izmir, Turkey

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Publications (96)209.14 Total impact

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    ABSTRACT: Sleep disorders (SDs) are common in cirrhotics and are often associated with hepatic encephalopathy. SDs negatively affect patients' daily activities and work efficiency. For this reason, early diognosis is important. The methods used for diagnosis of SDs are not practical and need longer periods of application and evaluation. In this study we aimed to investigate sleep disorders and related clinical parameters in liver cirrhosis and also want to investigate the using of Sleep Timing and Sleep Quality Screening questionnaire (STSQS), a simple form with a short application time, for diagnosis of SDs and its correlation with Pittsburg Sleep Quality Index (PSQI) form. Cirrhotic patients and age-matched healthy volunteers were enrolled. Patients were excluded from the study if they had neuropsychiatric disease or used excessive alcohol or drugs known to affect sleep. Both groups completed validated Turkish form of PSQI and STSQS. SD was defined as PSQI score (0-21) of >5 or STSQS≥5. 131 cirrhotic patients and 18 healthy volunteers were enrolled. SDs in cirrhotics and control group were detected 56.5% and 27.8% by PSQI, 49.6% and 16.7% by STSQS respectively, SDs is the most frequent in the Child C patients, and the least frequent in the Child A patients (p>0,05). No correlation was found between the MELD score and SDs. SDs were more common in cirrhotic patients with hypoalbuminemia and low hemoglobin levels. In addition, the patients with decompensated cirrhosis had more frequently SDs than the patients with compensated cirrhosis. In the patient group, sleep latency and total sleep time, sleep parameters were correlated with SDs. STSQS had statistical significant correlation with PSQI for diagnosis of SDs. SDs are common in cirrhotics and STSQS could be an appropriate and practical method for diagnosis of SDS in these patients. We can use it in cirrhotic patients at outpatient clinics. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 02/2014; · 3.87 Impact Factor
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    ABSTRACT: Background We aimed to measure the diurnal changes of critical flicker frequency in healthy subjects and cirrhotic patients and to investigate their relationship with sleep disturbance. Methods Cirrhotic patients and healthy volunteers were included. All groups completed the Pittsburgh Sleep Quality Index and a simple sleep questionnaire. Sleep disturbance was defined as a Pittsburgh Sleep Quality Index score of >5. Critical flicker frequency was measured twice a day to detect diurnal abnormalities. Results Overall, 59 cirrhotic patients (54.2% males, Mean Age 59 ± 11 years) and 18 controls (39.9% males, Mean Age 58 ± 9 years) were included. Sleep disturbances were more common in cirrhotics (66.1%) than controls (38.9%, p < 0.05). In cirrhotics, the critical flicker frequency was not related to decompensation. The nocturnal values were higher than the morning values in cirrhotics (64.4%), but not in controls (p < 0.0001). Additionally, sleep disturbances were more common in cirrhotics who had higher nocturnal values (p < 0.05). Conclusions Changes in the diurnal critical flicker frequency were observed in cirrhotics but not in controls. Sleep disturbances in cirrhotics appear to be associated with deviations of the diurnal rhythm of critical flicker frequency rather than with clinical parameters such as the clinical stages of cirrhosis and the Model For End-Stage Liver Disease and Child–Pugh scores.
    Digestive and Liver Disease. 01/2014;
  • Transplantation 02/2013; 95(3):e15-6. · 3.78 Impact Factor
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    ABSTRACT: Certain drugs including oxyphenisatin, methyldopa, nitrofurantoin, diclofenac, interferon, infliximab, pemoline, minocycline, atorvastatin, and rosuvastatin can induce hepatocellular injury that mimics autoimmune hepatitis. Whether drugs and herbs unmask or induce autoimmune hepatitis or simply cause a drug-induced hepatitis with accompanying autoimmune features is unclear. We describe the clinicopathologic details of eight cases with ornidazole-induced hepatitis with autoimmune features. Patients who presented with acute hepatitis between February 2001 and March 2009 were reevaluated for the etiology of liver disease. Patients with acute viral hepatitis, metabolic liver disease, vascular liver disease such as Budd-Chiari syndrome, biliary obstruction, or alcohol consumption were excluded. The autoimmune hepatitis scores, which were calculated at the time of diagnosis according to the criteria of the International Autoimmune Hepatitis Group, were recorded. In addition, the simplified criteria of the same group were applied retrospectively to each patient. Patients with ornidazole-induced toxic hepatitis with autoimmune hepatitis were included to constitute the study group of this report. All patients underwent initial liver biopsy, and one patient underwent liver biopsy three years later. All biopsies were scored according to the hepatitis scoring system by Ishak et al. (10). Overall, eight patients (all female) were diagnosed as drug-induced autoimmune hepatitis. With the exception of one patient, all were treated with prednisolone 30 mg/day + azathioprine 50 mg/day. The prednisolone dose was tapered according to the decrease in the level of transaminases. A two-year treatment program was planned for all patients. Ornidazole may cause drug-induced autoimmune hepatitis. Withdrawal of the drug may not provide the recovery despite a rather long wait. Thus, immunosuppressive therapy may be suggested in these cases.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 10/2011; 22(5):494-9. · 0.48 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
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    ABSTRACT: Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP-9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty-nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha-fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP-9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large-vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP-9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP-9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP-9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP-9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP-9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP-9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP-9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP-9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail.
    Liver Transplantation 05/2010; 16(5):621-30. · 3.94 Impact Factor
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    ABSTRACT: In patients with chronic hepatitis B (CHB) infection, precise definition of the hepatic fibrosis stage is the most important parameter to assess the risk of disease progression. Correlation between the prognosis of the CHB and the level of hepatitis-B virus DNA (HBV-DNA) is well considered in recent years. The aim of this study is to investigate the relationship between serum HBV-DNA level and histology of the liver. We also wanted to determine a threshold level of HBV-DNA for differentiation of low and high risk patients for progression. Two-hundred-fifty-nine patients with serum HBV-DNA level > 2000 copies/mL, determined by polymerase chain reaction (PCR), and biopsy proven naïve CHB infection were evaluated. Liver biopsies were evaluated histopathologically according to the Ishak scoring system. Laboratory values such as aspartate aminotransferase (AST), alanine aminotransferase ratio (ALT) were tested every 3 months and the highest value of each patient was evaluated. Mean age was 40 +/- 11 and 60% (155/259) of the patients were male. Mean laboratory values were as follows: AST: 52 +/- 46 U/L, ALT: 93 +/- 133 U/L, PLT: 224 +/- 60 1093)/l HBV DNA: 5.9 +/- 1.5 log copies/mL. In histological evaluation, mean inflammatory score was 4.34 +/- 2.72 and fibrosis score was 1.38 +/- 1.46. The fibrosis score was 0 or 1 in 63.3% (164/259) of the patients. The relationship between HBV-DNA level and histologic grade/stage was investigated and 15.000 copies/mL HBV DNA level was found as the threshold level to describe the activity of the disease. Fibrosis score was < 2 and/or grade < or = 5 in the patients who have HBV-DNA value below that level. In patients who have serum HBV-DNA level < or = 15000/copies/mL, histological activity was almost always low, and it seems that these patients do not need a liver biopsy regardless of hepatitis-B-e antigen (HBeAg) status.
    Hepato-gastroenterology 01/2010; 57(101):908-12. · 0.77 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
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    ABSTRACT: Although end of treatment virological responses are similar in posttransplant patients with recurrent chronic hepatitis C virus infection and nontransplant patients, the sustained virological response rate is lower in the posttransplant setting. We investigated the efficacy of a longer duration (3 years) of therapy. Thirteen patients with biopsy-proven recurrent hepatitis C were included in the study. In the first year of therapy, all patients were treated with a standard regimen of interferon alpha 2b 3MU 3 times in a week plus ribavirin (800 to 1000 mg/d). After the availability of pegylated interferon, patients were converted to pegylated interferon (1.5 microg/kg body weight). Hepatitis C virus RNA was evaluated at months 3, 6, 9, 12, 24, 36, and 42. If hepatitis C virus RNA was negative at month 12, the patients continued treatment for 36 months. Hepatitis C virus RNA was negative in six patients at 12 months, including two who became hepatitis C virus RNA negative after 3 months; two, after 6 months; and two, after 12 months of therapy. Those six continued treatment completing 3 years of treatment with a sustained virological response. Four of those six patients with sustained virological response required colony-stimulating factors during treatment. Although the hepatitis C virus RNA status of patients at 12 weeks is a good marker to predict a sustained virological response in the nontransplant setting, it is not valid in posttransplant patients. A prolonged duration of therapy for patients who are viral responders at 12 months may prevent recurrence and increase the sustained virological response rate.
    Transplantation Proceedings 11/2009; 41(9):3806-9. · 0.95 Impact Factor
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    ABSTRACT: To investigate the macrophage migration inhibitory factor (MIF) expression and -173 G/C polymorphism of the MIF gene in nonalcoholic fatty liver disease (NAFLD). Ninety-one patients with diagnosis of NAFLD and 104 healthy controls were included in the study. MIF -173 G/C polymorphism was detected using the PCR-restriction fragment length polymorphism based method. NAFLD was stratified as nonalcoholic steatohepatitis (NASH), probable NASH and steatosis, respectively in groups 1, 2 and 3, according to NAFLD Activity Score. MIF expression was detected by immunohistochemistry staining. Mean age of the patients was 50.1+/-9.6 years, and 54 of them were male. Serum alanine aminotransferase and aspartate aminotransferase were 50/83, 42/63 and 31/32, respectively in groups 1, 2 and 3, (P<0.05). Both the MIF expression of hepatocytes and mononuclear cells were more prominent in groups 1 and 2 than group 3. There was no correlation between MIF expression of hepatocytes and fibrosis stage. However, MIF expression of mononuclear cells significantly increased according to fibrosis stage (P<0.05, R : 0.2). There was no significant correlation between MIF genotype and MIF expression in the liver. MIF expression is significantly increased especially by mononuclear cells in liver tissue of patients with NASH secondary to inflammation. Thus, it should be considered as a consequence not a causal factor.
    European journal of gastroenterology & hepatology 10/2009; 22(2):192-8. · 1.66 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2009; 50.
  • Journal of Hepatology - J HEPATOL. 01/2009; 50.
  • Sinan Akay, Zeki Karasu
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    ABSTRACT: Post-transplant hepatitis B virus (HBV) recurrence prophylaxis is a sine qua non of liver transplantation for HBV-related liver disease because of high rate and aggressive course of HBV recurrence. Hepatitis B immune globulin (HBIG) is a polyclonal immune globulin solution obtained from plasma, donated by individuals with high titres of anti-HBs (hepatitis B antibody). Although it was being used for postexposure prophylaxis against HBV since 1974, its use in post-transplant prophylaxis of HBV infection was not until 1987. Long-term prophylaxis with HBIG alone had been the standard treatment in post-transplant HBV prophylaxis until the introduction of lamivudine. Combining HBIG with oral nucleotide/nucleoside analogues in post-transplant prophylaxis of recurrent HBV resulted in lower recurrence rates of infection. However, high cost and emergence of immune escape mutations are still the problems to be solved regarding HBIG therapy in post-transplant prophylaxis of HBV recurrence.
    Expert opinion on biological therapy 12/2008; 8(11):1815-22. · 3.22 Impact Factor
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    ABSTRACT: Toxoplasmosis is a serious and potentially life-threatening disease in liver transplant recipients while they are immunosuppressed. We report the clinical and laboratory findings related to active toxoplasma infection associated with 40 immunosuppressed liver transplant procedures that took place over a 12-month period at a major transplant unit in Izmir, Turkey. Twenty-seven (67.5%) of the 40 transplant recipients were found to be seropositive for toxoplasma infection and therefore at risk of reactivated infection. From the serological status of the donors, which was ascertained in 38 of 40 cases, we identified 3 (7.9%) of 38 transplants to be from a seropositive donor to a seronegative recipient. In 10 (26.3%) of 38 transplants, both the donor and recipient were seronegative, and this excluded toxoplasma as a risk. A comparison of real-time polymerase chain reaction (PCR) and nested PCR was undertaken in combination with a range of serological assays (the Sabin-Feldman dye test, enzyme immunoassay immunoglobulin M, and immunosorbent agglutination assay immunoglobulin M). Ethylene diamine tetraacetic acid blood samples from 3 of the 30 recipients at risk from toxoplasma were found positive by PCR, but only 1 of these was found positive in both assays. Among the 3 PCR-positive patients, immunoglobulin M and immunoglobulin G antibody levels increased in only 1 patient. Correlations between symptoms, laboratory findings, and clinical management (use of anti-toxoplasma therapy) are presented. Our findings suggest that toxoplasma presents a significant risk to our liver transplant population and that PCR is a helpful addition in identifying active infections and hence in informing clinical management decisions.
    Liver Transplantation 11/2008; 14(10):1526-32. · 3.94 Impact Factor
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    ABSTRACT: Ascites is one of the main features of liver decompensation in cirrhosis, and it is considered to be a dynamic process. In this study, we aimed to (1) measure the reabsorption rate of ascites; (2) evaluate whether these findings were related to features of ascites, hemodynamics, and serum measurements; and (3) examine morphologic changes in the diaphragm of cirrhotic patients. In all, 42 cirrhotic patients with ascites were enrolled in the study to comprise our study group. Using the dextran 70 test, patient ascites volumes and reabsorption rates were measured. Biopsies from the peritoneal side of the diaphragm were also processed for scanning electron microscopy and lymphatic immunohistochemical studies from the cirrhotic patients and control cadavers. The mean ascites reabsorption rate was 4.5 +/- 4.5 (0.18-14.6) mL/min, which correlated significantly with the calculated ascites volume (r = 0.75, P < 0.001). The mean ascites viscosity was 1.07 +/- 0.07 (0.99-1.17) centipoise, which demonstrated a high degree of negative correlation with the ascites reabsorption rate (r = -0.77, P < 0.001). Patients with a history of spontaneous bacterial peritonitis had significantly lesser ascites reabsorption rates than patients without this particular history. The size of lymphatic stomata in scanning electron microscopy depictions was increased, and lymphatic lacunae were dilated in immunohistochemical studies in the cirrhotic patients with ascites. However, these findings were not uniform in every cirrhotic patient with ascites. The volume and viscosity of ascites seem to influence its reabsorption rate. Additionally, previous episodes of spontaneous bacterial peritonitis may be responsible for the decreased ascites reabsorption rates observed in certain patient populations.
    Translational Research 10/2008; 152(4):157-64. · 3.49 Impact Factor
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    ABSTRACT: Pretransplantation clearance of hepatitis C virus (HCV)-RNA reduces the risk of HCV recurrence after transplantation. Furthermore, a sustained virological response could reduce disease progression and slow clinical deterioration in nontransplanted patients. To evaluate the safety, tolerability and efficacy of pegylated-interferon (PEG-IFN) alfa-2a plus ribavirin therapy in HCV-related decompensated cirrhotics. Twenty HCV-related decompensated cirrhotics (44-67 years, 12 males, six Child-Pugh score A, 14 Child-Pugh score B, all with genotype 1b) were enrolled into the study. Treatment with PEG-IFN alfa-2a (135 microg, once a week) plus ribavirin (1000-1200 mg/day) was commenced. A 48-week treatment was planned in patients who had early virological response. Treatment was stopped in 8 (40%) patients. The remaining 12 (60%) patients completed 48 weeks of therapy; nine (45%) of them obtained end-of-therapy virological response and six (30%) of them obtained sustained virological response. Living donor liver transplantation was performed in three (15%) patients. Eight (40%) and six (30%) patients needed to reduce PEG-IFN alfa-2a and ribavirin dosages, respectively. No patient died during the follow-up period. PEG-IFN alfa-2a plus ribavirin therapy is safe, tolerable and efficacious in selected HCV-related decompensated cirrhotics.
    Alimentary Pharmacology & Therapeutics 07/2008; 27(11):1081-5. · 4.55 Impact Factor
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    ABSTRACT: Hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrences affect both patient and graft survivals post-orthotopic liver transplantation (OLT) in HBV patients with HCC. We analyzed the relationship between HBV and HCC recurrence in a large cohort of HBV-OLT patients with versus without HCC. Two hundred eighty-seven HBV patients with OLT (72 also with HCC) were included in the study. Mean follow-up in the post-OLT period was 31.7 +/- 24.7 (range, 3-119) months. Post-OLT HBV recurrence observed in 10.1% of patients was more prevalent among the HCC group; 23.6% versus 5.5% in patients with and without HCC, respectively. The mean interval for the development of HBV recurrence was 39.5 +/- 28.5 (range, 2-99) months. Among 72 HCC patients, 8 patients (11.1%) had recurrent HCC, and 7 of them also had HBV recurrence. The mean interval for the development of HCC recurrence was 11.2 +/- 7.85 (range, 2-23) months after OLT. OLT patients with HCC with tumors exceeding the Milan criteria had worse 1-, 3-, and 5-year survival rates than patients with HCC meeting the Milan criteria. HBV and HCC recurrence-free survivals were significantly lower in patients with HCC and HBV recurrence, respectively. In the 7 patients with both HCC and HBV recurrence, mean HBV recurrence time was 9.42 +/- 6.75 months and mean HCC recurrence time was 9.57 +/- 6.75 months. There was a strong correlation between HBV and HCC recurrence times. Cox proportional hazards regression analysis showed that only HCC recurrence was a significant independent predictor of HBV recurrence (P < .001; hazard ratio [HR] = 26.94; 95% confidence interval [CI] = 10.81-67.11). On the other hand, HBV recurrence (P = .013; HR = 5.80; 95% CI = 1.45-23.17) and nodule count (P = .014; HR = 13.08; 95% CI = 1.70-100.83) were significant predictors of HCC recurrence. HBV and HCC recurrences demonstrate a close relationship in patients with OLT.
    Transplantation Proceedings 06/2008; 40(5):1511-7. · 0.95 Impact Factor
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    ABSTRACT: Cytokines play important roles in the regulation of immune response. The aim of the study was to investigate the association of the cytokine gene polymorphisms with persistence of hepatitis B virus (HBV) infection and the development of end-stage liver disease (ESLD) due to HBV infection. The study involved 27 patients with end-stage liver disease due to HBV infection, 23 HBV carriers and 60 healthy controls. All genotyping (TNF-alpha, TGF-beta, IL-10, IFN-gamma) experiments were performed using sequence specific primers (PCR-SSP) by using commercial kit according to manufacturers' instructions. The frequencies of TNF-alpha -308 G/G and TGF-beta1 codon 10-25 T/C-G/G polymorphisms were significantly higher in HBV-infected individuals (patients+carriers) when compared with those of healthy controls (p: 0.02 and p: 0.004, respectively). The frequency of TNF-alpha -308 G/G polymorphism was significantly higher in the patients than those of the healthy controls (p: 0.02), whereas the frequency of TGF-beta1 codon 10-25 T/T-G/G polymorphism was lower (p: 0.028). On the other hand, TNF-alpha -308 G/G and TGF-beta codon 10-25 T/C-G/G polymorphisms were significantly more common in HBV carriers than the control group (p: 0.017 and p: 0.018, respectively). In addition, TNF-alpha -308 G allele frequency was significantly more common in HBV-infected individuals (patients+carriers) than those of healthy controls (p: 0.0007). TNF-alpha -308 G allele frequency was also found to be higher in patients or carriers when compared with those of healthy controls (p: 0.01 and p: 0.01, respectively). Statistically significant differences were still kept after Bonferroni correction of the p-values for only TNF-alpha -308 G allele frequency in patients or carriers (Pc). Our study suggests that TNF-alpha gene polymorphism in patients infected with HBV would result in relatively inefficient inhibition of HBV and development of ESLD, and therefore, may be valuable predictor determinants for the development of ESLD in patients with chronic HBV infection.
    Infection Genetics and Evolution 02/2008; 8(1):20-5. · 2.77 Impact Factor